It is the primary objective of this research program to determine the cause of photoreceptor degeneration in inherited animal disorders and to relate discoveries in animal disorders to specific diseases that cause blindness in humans. We intend to realize our objectives by systematically investigating three individual but interrelated projects. The first relates to animals that become afflicted with visual cell degeneration at or near the postnatal age when photoreceptor cells are differentiating. At least three of these disorders (rd mouse, Irish setter dog and collie dog) have an abnormality in cyclic GMP metabolism that apparently initiates the degenerative process. In this project we delve more deeply into the mechanisms that cause the abnormality in cyclic GMP metabolism and seek a method for diagnosing the disorder in living animals. The second project relates to animals that become afflicted with a slow process of visual cell degeneration; visual loss begins later in life and after the photoreceptor cells are mature. We are testing the hypothesis that these visual cells degenerate as a consequence of their inability to metabolize free radicals arising from metabolic or photodynamic reactions. The third project relates to the acquisition and analysis of biochemical parameters within morphologically defined regions of the human retina. We are developing data which will establish the normal range of constituents (cyclic nucleotides, amino acids, etc.) within human visual cells. This data will provide a standard to which similar data from diseased human retina can be compared, and it will facilitate the assessment of whether some animal disorders share common characteristics with those of specific human disease. It is envisioned that this interdisciplinary approach will disclose the cause of visual cell degeneration in several animal disorders and that these findings will advance our understanding of human diseases that cause blindness.